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PubMed2003

[Sacral root neuromodulation for the treatment of urinary incontinence reported to detrusor hyperactivity].

BACKGROUND AND PURPOSE: This paper reviews therapeutic sacral neuromodulation for treating urinary urge incontinence related to detrusor hyperactivity. METHODS: We reported data from our department and from the international literature on topics such as the physiological basis of neuromodulation, techniques of testing, chronic implantation and clinical results. RESULTS: In an intention to treat analysis , neuromodulation results varied from 21.5 to 25% globally. On implanted patients, the response rate varied from 40 to 88% and was stable. Sub-chronic test morbidity was very rare. Surgical revision rate was reported from 6.25 to 37.7%. CONCLUSIONS: Neuromodulation strongly ameliorates approximately a third of all the patients with urge urinary incontinence due to detrusor hyperactivity. New technical improvements should lead to better results in the future.

Electric Stimulation Therapy↗

PubMed2003

[Continuous bilateral sacral neuromodulation as a minimally invasive implantation technique in patients with functional bladder changes].

OBJECTIVE: Up to 50% of patients with bladder dysfunctions undergoing sacral neuromodulation treatment are non-responders. The most common treatment method today is the implantable neuromodulation system described by Tanagho and Schmidt; which allows unilateral sacral nerve stimulation. Our aim was to increase the number of responders and to improve the general efficiency of chronic sacral neuromodulation; therefore we have developed the bilateral electrode implantation by minimally invasive laminectomy. METHODS: PNE-tests were carried out to assess which patients were likely to be good responders. Thirty patients (16 with detrusor instability, 14 with hypocontractile detrusors) were subjected to minimally invasive laminectomy and received implants of bilateral electrodes. RESULTS: In those patients with a hyopcontractile detrusor, the level of residual urine of initially 350 ml was reduced to 58 ml, and the maximum detrusor pressure during micturition increased from initially 12 cMH2O to 34 cmH2O. In the other patient group with detrusor instability, the average number of incontinence incidences could be reduced from initially 7.2 to 1 per day, while the bladder capacity rose from 198 ml to 348 ml. The modulation effect did not show any signs of deteriorating in any of the patients. The follow-up period was 28 months on average. CONCLUSIONS: Clinical experience has shown that optimal neuromodulation in patients with bladder dysfunction can be achieved by this new approach involving bilateral electrode implantation. Moreover, the laminectomy implantation method guarantees a minimum of invasive trauma and enables optimal placement and fixation of the electrode.

Electric Stimulation Therapy↗

PubMed1987

Neuromodulators and respiratory control in the infant.

In this review some of the neuromodulators involved in respiration control are discussed with special regard to the newborn. The term neuromodulator is defined relatively widely herein. Various types of neuromodulators have been found to affect respiratory control. These effect are more pronounced in the fetus and the neonate than in the adult. A disturbed balance between excitatory and inhibitory neuromodulators is postulated as causing the instability of respiratory control often seen in infants.

Adenosine↗

PubMed1996

Transcutaneous electrical nerve stimulation and temporary S3 neuromodulation in idiopathic detrusor instability.

PURPOSE: We studied the effects of electrical stimulation on idiopathic detrusor instability. MATERIALS AND METHODS: Between January 1993 and December 1994, 30 men and 41 women (mean age plus or minus standard deviation 48 +/- 16 years) underwent transcutaneous electrical nerve stimulation (TENS) of the S2-S3 dermatomes, and 13 men and 22 women (mean age 48 +/- 12 years) underwent S3 neuromodulation. Subjective assessment was performed using a diary and symptom score of 0 to 14. Objective outcome was analyzed with urodynamic studies. RESULTS: Mean duration of TENS was 3 +/- 1 weeks (range 2 to 4). Although there were no major complications 31% of the patients reported local skin irritation. The overall urinary symptom scores improved from 10 +/- 2 (range 5 to 14) before the study to 7 +/- 3 (range 1 to 14) during stimulation. Urodynamic analysis revealed significant (p < 0.05) improvements in total bladder capacity and voided volume, and decreases in the number and frequency of unstable contractions. Mean duration of S3 neuromodulation was 6 +/- 1 days (range 4 to 8 days). Four procedures failed due to electrode displacement in 3 cases and procedure intolerance in 1. Hemorrhage from the puncture site occurred in 1 patient. Overall urinary symptom scores were 10 +/- 3 (range 5 to 14) before the study and 5 +/- 2 (range 2 to 10) during stimulation. Although symptomatic relief was more pronounced with S3 neuromodulation, no statistically significant differences were found regarding urinary symptoms compared to TENS. CONCLUSIONS: In patients with severe detrusor instability refractory to conservative treatments the use of TENS and S3 neuromodulation produced significant changes in urodynamic parameters and presenting symptoms. Our results appear to justify evaluation with neuromodulatory techniques before definitive surgical intervention in these patients.

Electric Stimulation Therapy↗

PubMed2026

Sacral Neuromodulation in the Management of Refractory Pediatric Lower Urinary Tract Dysfunction.

INTRODUCTION: Sacral neuromodulation is currently used in the pediatric patient population for refractory lower urinary tract dysfunction (LUTD). Evidence, however, is currently limited for institutional experiences of long-term outcomes for sacral neuromodulation in the pediatric patient population. OBJECTIVE: The objective of this study is to perform a retrospective review of a large multi-institutional cohort of pediatric patients that underwent sacral neuromodulation (SNM) for refractory LUTD, focused on rates of symptom improvement, quality of life, and bowel-bladder dysfunction measures following device implantation. Secondary objectives included assessing device complication rates and device removals due to failure or successful resolution of symptoms. METHODS: We performed a retrospective cohort study of pediatric patients at three children's hospitals that underwent SNM device implantation for refractory LUTD. Patients 4-18 years of age who were diagnosed with refractory LUTD and managed at a participating institution with follow-up were included. Outcomes were evaluated at baseline and post-operatively after two-stage device implantation at initial follow-up and annually until device removal or final follow-up. RESULTS: From 2010 to 2022, a total of 205 children underwent SNM procedures at three pediatric hospital centers. 204 patients completed the two-stage procedure for permanent device implantation with a median follow-up of 3.4 years (1.3, 4.9). One hundred seventy-eight patients reported partial (25%) or complete (54%) device response/symptom improvement by final follow-up. Comparison of patient-reported validated questionnaires completed at baseline and by final follow-up visit revealed significant improvement in median Pediatric Quality of Life Inventory (PedsQL) (p = 0.004) and Vancouver Nonneurogenic Lower Urinary Tract Dysfunction/Dysfunctional Elimination Syndrome bowel-bladder dysfunction (BBD) scores (p < 0.001). Of those with any device complication (n = 43;21%), 19 patients required device revision, and 20 required complete device removal. Separately, twenty-eight patients (13%) underwent device removal due to resolution of symptoms or treatment success at a median period of 5 years (4,7). CONCLUSION: SNM use demonstrated a majority of patients reporting at least partial subjective symptom improvement following device implantation across multiple institutions by final follow-up. SNM is a viable treatment option for refractory LUTD in the pediatric patient if willing to undergo an invasive procedure and in which thorough counseling of risks and benefits has occurred.

Humans↗

PubMed1996

Neuropeptide localization in varicosities of Aplysia sensory neurons is regulated by target and neuromodulators evoking long-term synaptic plasticity.

The synapses between the sensory neuron (SN) and motor neuron of Aplysia undergo long-term functional and structural modulation with appropriate behavioral training or with applications of specific neuromodulators. Expression of molecules within the presynaptic terminals may be regulated in parallel with the changes evoked by the neuromodulators. We examined with immunocytochemical methods whether the level of sensorin, the SN-specific neuropeptide, is modulated in SN varicosities by the location of interaction with the target motor cell L7 and by applications of either 5-HT that evoke long-term facilitation or FMRFamide that evoke long-term depression of Aplysia sensorimotor connections in vitro. A significantly higher proportion of SN varicosities are sensorin positive when they are in contact with the proximal axons of L7 compared to varicosities of the same SNs in contact with distal L7 neurites. Both 5-HT and FMRFamide evoked changes in the efficacy and structure of sensorimotor connections that are accompanied by changes in the frequency of sensorin-positive varicosities contacting the axons of L7. More preexisting SN varicosities are stained after 5-HT, and fewer preexisting SN varicosities are stained after FMRFamide. These results suggest that the postsynaptic target and the neuromodulators not only regulate overall structure but also regulate the level of SN neuropeptide at synaptic sites.

Animals↗

PubMed2001

Neuromodulator content of hamster intergeniculate leaflet neurons and their projection to the suprachiasmatic nucleus or visual midbrain.

The intergeniculate leaflet (IGL) of the lateral geniculate complex has widespread, bilateral, and reciprocal connections with nuclei in the subcortical visual shell. Its function is poorly understood with respect to its role in visual processing. The most well-known IGL projection, and the only one with a clear function, is the geniculohypothalamic tract (GHT) that terminates in the suprachiasmatic nucleus (SCN), site of the primary circadian clock. The hamster GHT is derived, in part, from IGL neurons containing neuropeptide Y and enkephalin. IGL neurons containing these peptides also project to the pretectal region. The present studies used a combination of immunohistochemical, lesion, and retrograde tracing techniques to study neuron types in the IGL and their projections to hamster SCN and pretectum. Two additional neuromodulators, gamma-aminobutyric acid (GABA) and neurotensin, are shown to be present in IGL neurons. The GABA- and neurotensin-immunoreactive neurons project to the SCN with terminal field patterns very similar to those for neuropeptide Y and enkephalin. IGL neurons of all four types also send projections to the pretectum, but rarely do individual cells project to both the SCN and the pretectum. Nearly all neurotensin is colocalized with neuropeptide Y in IGL neurons, although about half of the neuropeptide Y cells do not contain neurotensin. Otherwise, the extent to which the four neuromodulators are colocalized varies from 6% to 54%. Nearly every SCN neuron appears to contain GABA. In the IGL, the majority of cells studied are not identifiable by GABA immunoreactivity. Putative functions of the various neuromodulator projections from the IGL to pretectum or SCN are discussed.

Animals↗

PubMed2005

Chronic pudendal nerve neuromodulation in women with idiopathic refractory detrusor overactivity incontinence: results of a pilot study with a novel minimally invasive implantable mini-stimulator.

AIMS: To assess the results of chronic pudendal nerve neuromodulation with a novel technique in a pilot study on women with idiopathic refractory detrusor overactivity incontinence. MATERIALS AND METHODS: A percutaneous screening test (PST) was performed in patients with urodynamically demonstrated detrusor overactivity incontinence. Such a test includes the performance of a cystometrogram without and with percutaneous pudendal nerve stimulation and is considered positive if stimulation results in a more than 50% increase in the bladder volume at the first involuntary detrusor contraction or the maximum cystometric capacity. Patients with a positive PST qualified for the implantation of a mini-neurostimulator with an integrated electrode, a so-called bion(R), adjacent to the pudendal nerve at Alcock's Canal. Five-day voiding-incontinence diaries were the main tool for the evaluation of therapy. RESULTS: A PST was performed in 14 women. Six patients responded positively and received a bion. The degree of incontinence decreased significantly in this group, which also included patients in whom sacral neuromodulation had failed. There were no severe adverse events. CONCLUSIONS: Chronic pudendal nerve stimulation may reduce the degree of detrusor overactivity incontinence, even in patients in whom sacral neuromodulation fails. Bion therapy is relatively simple and minimally invasive and is well tolerated by the patient.

Adult↗

PubMed2007

In patients undergoing neuromodulation for intractable urge incontinence a reduction in 24-hr pad weight after the initial test stimulation best predicts long-term patient satisfaction.

AIMS: To evaluate long-term patient satisfaction of sacral neuromodulation and to correlate satisfaction with incontinence parameters. METHODS: Patients at least 1-year remote from sacral neuromodulation were mailed a questionnaire to evaluate satisfaction and assess incontinence symptoms. RESULTS: Fifty-two patients were consecutively enrolled in the study. Forty-nine questionnaires (94.2%) were returned. The average interval between implantation and questionnaire completion was 27.2 (range 12-52) months. 83.7% of respondents were satisfied and 79.6% of patients would "do it all over again." Compared to dissatisfied subjects during test stimulation, the satisfied patients had a significant decrease in 24-hr pad weight (84.5% vs. 60.6%, P = 0.002) but did not differ in daily pad usage (4.5 fewer pads per day vs. 3.4, P = 0.190). At long-term follow-up, satisfied patients noted significantly greater improvement in their Incontinence Impact Questionnaire score versus dissatisfied patients (mean improvement 53 vs. 10 points, P = 0.0003). Using multiple logistic regression, change in 24-hr pad weight, but not change in average daily pad usage, was correlated with long-term satisfaction. CONCLUSIONS: Eighty-four percent of patients were satisfied with sacral neuromodulation at a mean of 27 months. An 84.5% reduction in 24-hr pad weight correlated with long-term patient satisfaction. In addition to lack of efficacy, device pain was a contributing factor to dissatisfaction.

Aged↗

PubMed1989

Effect of putative neuromodulators on rhythmic buccal motor output in Lymnaea stagnalis.

The effects of a variety of neuromodulator substances on rhythmic motor output and activity in neurons in the feeding circuitry of Lymnaea stagnalis were examined. Each neuromodulator produced a unique combination of effects at different levels in the network: i.e., pattern-generating interneurons (N1, N2, and N3), an identified higher-order interneuron (cerebral giant cell, CGC), and buccal motoneurons. 5-Hydroxytryptamine, acetylcholine, and FMRFamide all inhibited rhythmic motor activity. However, this was achieved in different ways. Dopamine changed the nature of rhythmic activity from one in which N2 interneuronal activity was predominant ("N2 rhythm") to a feeding rhythm. Dopamine was the only substance capable of activating the feeding rhythm. Activity in the CGC was increased by 5-hydroxytryptamine, dopamine, and acetylcholine and reduced by FMRFamide. Differential responses in buccal motoneurons were also observed. The results are discussed in relation to previous work on other species and also in terms of the selection of different patterns of motor output by neuromodulators.

Acetylcholine↗

PubMed2002

Change of vanilloid receptor 1 following neuromodulation in rats with spinal cord injury.

BACKGROUND: Neuromodulation has been used to treat voiding dysfunction caused by spinal cord injury (SCI). However, the underlying mechanism of this technique is not well understood. Recently, vanilloid receptor 1 (VR1) has been recognized as a capsaicin receptor and an agent for noxious stimuli. The purposes of this study were to evaluate whether development of bladder hyperreflexia after SCI involves VR1 upregulation and whether VR1 is involved in the process of neuromodulation. MATERIALS AND METHODS: Sprague-Dawley rats (n = 20) were divided into five groups: sham control (n = 4); 3 days after SCI (n = 4); 7 days after SCI (n = 4); 14 days after SCI (n = 4), and 14 days after SCI with neurostimulation (n = 4). Bilateral electrode wires were implanted into S1 dorsal foramina and electrical stimulation was performed 8 h/day for 2 weeks. Spinal segments of L6, S1, and dorsal root ganglia were removed and cut into sections. The intensity of VR1 staining was evaluated by image analysis. RESULTS: VR1-positive staining was confined to the superficial dorsal horn of the spinal cord. The staining was weak in the sham group (1/luminosity: 0.0050 +/- 0.0006), but the staining intensity was significantly increased in three SCI groups (3 days, 7 days, and 14 days) when compared with that in the sham group (P < 0.05). After neuromodulation, the staining intensity was reduced. CONCLUSIONS: VR1 expression in the spinal cord is up-regulated after SCI. Sacral nerve root stimulation can down-regulate the VR1 expression.

Animals↗

PubMed1991

Neuromodulators of the lingual von Ebner gland: an immunocytochemical study.

The serous lingual glands of von Ebner secrete lingual lipase, an enzyme that begins fat digestion in the stomach. The objective of this study was to characterize the neuromodulators in the rat tongue and von Ebner glands using immunocytochemical techniques. Rat lingual tissues were fixed in formalin, embedded in paraffin and sectioned at 4 microns for light microscopic studies. Immunocytochemical localization of neuromodulators was performed with monospecific anti-rat neuromodulator IgG or control (preimmune) IgG as the primary antibody, using the peroxidase-antiperoxidase (PAP) technique. No staining was seen with control anti-rat IgG. Immunospecific staining for vasoactive intestinal peptide (VIP), tyrosine hydroxylase and choline acetyltransferase (CHAT) was observed in nerves in the tongue, and cells containing immunospecific staining for serotonin (5-hydroxytryptamine) were seen in the stroma between the lingual glands. Selected cells in the serous glands stained positively for the presence of substance P and somatostatin. Adrenergic, VIP-containing and cholinergic nerves appear to innervate the tongue and serous glands. Substance P and somatostatin were identified in cells of the lingual serous glands and may be additional local modulators regulating lingual lipase release.

Animals↗

PubMed2003

[Sacral neuromodulation in treatment of functional disorders of the lower urinary tract. An overview of basic principles, indications, outcomes].

Over the last few years, sacral neuromodulation has become an established treatment option for dysfunctions of the lower urinary tract. It fills the gap that used to exist between conservative therapy and costly invasive methods such as urinary drainage via a deactivated bowel segment. Initially, the clinical value of sacral neuromodulation was controversial even among neurourologists. This was mainly due to a lack of understanding of the physiological processes, uncertain diagnostics, the design of the hardware, and a surgical topography relatively unknown to the urologist. In the meantime, however, sacral neuromodulation has become a standard part of clinical routine with respect to the treatment of dysfunctions of the lower urinary tract, and it is regularly employed in various urological institutions across Europe and the USA. This form of treatment, which is the final straw for patients who believed themselves-after many frustrated therapy attempts-to be "hopeless cases," can now also successfully be employed as an ambulatory measure. The latest data from our hospital, as well as contributions presented at the last DGU Congress in Wiesbaden, indicate that patients with neurogenic urinary retention are the most likely to profit from this treatment option.

Electric Stimulation Therapy↗

PubMed2004

Neuromodulation for behavior in the locust frontal ganglion.

Neuromodulators orchestrate complex behavioral routines by their multiple and combined effects on the nervous system. In the desert locust, Schistocerca gregaria, frontal ganglion neurons innervate foregut dilator muscles and play a key role in the control of foregut motor patterns. To further investigate the role of the frontal ganglion in locust behavior, we currently focus on the frontal ganglion central pattern generator as a target for neuromodulation. Application of octopamine, a well-studied insect neuromodulator, generated reversible disruption of frontal ganglion rhythmic activity. The threshold for the modulatory effects of octopamine was 10(-6) mol l(-1), and 10(-4) mol l(-1) always abolished the ongoing rhythm. In contrast to this straightforward modulation, allatostatin, previously reported to be a myoinhibitor of insect gut muscles, showed complex, tri-modal, dose-dependent effects on frontal ganglion rhythmic pattern. Using a novel cross-correlation analysis technique, we show that different allatostatin concentrations have very different effects not only on cycle period but also on temporal characteristics of the rhythmic bursts of action potentials. Allatostatin also altered the frontal ganglion rhythm in vivo. The analysis technique we introduce may be instrumental in the study of not fully characterized neural circuits and their modulation. The physiological significance of our results and the role of the modulators in locust behavior are discussed.

Action Potentials↗

PubMed2005

Preliminary results of peripheral transcutaneous neuromodulation in the treatment of idiopathic fecal incontinence.

PURPOSE: Few therapeutic tools are available for treating idiopathic anal incontinence. Sacral neuromodulation appears to be effective in selected patients but requires surgical implantation of a permanent electrical stimulator. The aim of this work was to assess the efficiency of posterior tibial nerve (PTN) transcutaneous electrical nerve stimulation (TENS) in the treatment of anal idiopathic incontinence. METHODS: Ten women were treated by PTN TENS, 20 min a day for 4 weeks. Functional results were evaluated by Wexner's incontinence score and anorectal manometry. RESULTS: Eight of the ten patients showed a 60% mean improvement of their incontinence score after 4 weeks. This improvement remained stable over the 12-week follow-up period. Manometric parameters did not differ before and after stimulation. CONCLUSION: PTN neuromodulation without surgically implanted electrode could represent a safe and low-cost alternative to permanent sacral neuromodulation for idiopathic anal incontinence.

Adult↗

PubMed2005

Sacral neuromodulation in treatment of fecal incontinence following anterior resection and chemoradiation for rectal cancer.

PURPOSE: Fecal incontinence may occur in patients who have undergone anterior resection for rectal cancer without presenting sphincter lesions. Chemoradiation may contribute to disrupting continence mechanisms. Treatment is controversial. Assessment of fecal incontinence in patients who agreed to integrate treatment for rectal cancer and treatment with sacral neuromodulation are reported. METHODS: Fecal incontinence following preoperative chemoradiation and anterior resection for rectal cancer was evaluated in four patients. A good response was observed during the percutaneous sacral nerve evaluation test, and so permanent implant of sacral neuromodulation system was performed. Reevaluation was performed at least two months after implant. RESULTS: After device implantation, the mean fecal incontinence scores decreased, and the mean number of incontinence episodes dropped from 12.0 to 2.5 per week (P < 0.05). Permanent implant resulted in a significant improvement in fecal continence in three patients, and incontinence was slightly reduced in the fourth. Manometric parameters agreed with clinical results: maximum and mean resting tone and the squeeze pressure were normal in three patients and reduced in one. In these same three patients, neorectal sensation parameters increased when the preoperative value was normal or below normal and decreased when the preoperative value was higher than normal, whereas in one patient in whom extremely low values were recorded all of the parameters decreased significantly. CONCLUSIONS: Fecal incontinence following anterior resection and neoadjuvant therapy should be carefully evaluated. If a suspected neurogenic pathogenesis is confirmed, sacral neuromodulation may be proposed. If the test results are positive, permanent implant is advisable. Failure of this approach does not exclude the use of other, more aggressive treatment.

Combined Modality Therapy↗

PubMed2002

Sacral neuromodulation for the treatment of bladder dysfunction.

S3 nerve root neuromodulation is becoming an accepted therapy for individuals afflicted with lower urinary tract symptoms, such as idiopathic urinary urge incontinence, frequency, urgency, and urinary retention, who fail current standard therapies. This patient population is difficult to treat, and this therapy offers an option that can restore quality of life to these individuals. While the precise pathophysiologic mechanisms underlying these voiding symptoms is unknown based on the physiology of bladder function, it is logical to conclude that they relate to some aberration of the neuromuscular apparatus of the bladder and/or its outlet (the urethra). These pathophysiologic defects are not overtly manifested outside the lower urinary tract because these patients routinely do not have any apparent neurologic deficits. The fact that S3 neuromodulation can clinically improve these lower urinary tract symptoms would support the notion that the neural regulation of the bladder is somehow altered in these patients. This paper presents a review of the current knowledge regarding sacral neuromodulation in treatment of non-neurogenic voiding dysfunction.

Electric Stimulation Therapy↗

PubMed2002

[Chronic sacral bilateral neuromodulation. Using a minimal invasive implantation technique in patients with disorders of bladder function].

The implantable neuromodulation system described by Tanagho and Schmidt enables unilateral sacral nerve stimulation. Reports have been made on sacral neuromodulation failures of up to 50% in patients undergoing this procedure. We chose the bilateral electrode implantation and a minimal invasive laminectomy to ensure a more effective modulation and better placement and fixation of the electrodes. After successful assessment using a peripheral nerve evaluation test, 20 patients (14 with detrusor instability, 6 with hypocontractile detrusor) underwent minimally invasive laminectomy and bilateral electrode placement. In the patients with detrusor instability, the incontinence episodes were reduced from 7.2 to 1 per day and the bladder capacity improved from 198 to 352 ml. In patients with hypocontractile detrusor, the initial residual urine level of 450 ml dropped to 108 ml. Maximum detrusor pressure during micturition rose from 12 cmH2O initially to 34 cmH2O. The average follow up period was 17.5 months. There was no sign of deterioration in the modulation effect in any of the patients. Bilateral electrode implantation and the new sacral approach allow optimal neuromodulation in patients with bladder dysfunction. Laminectomy enables optimum electrode placement and fixation with minimal trauma.

Electric Stimulation Therapy↗